Scientists at the Center for Infectious Disease Research (CIDR) in Seattle, Washington recently uncovered a critical piece in the puzzle of how malaria parasites infect their host. The work, published online on November 27, 2015 in Science, reveals the details of how the malaria parasite invades its initial target organ, the liver. The Science article is titled “Malaria Parasites Target the Hepatocyte Receptor EphA2 for Successful Host Infection." Without infection of the liver, the parasites cannot multiply or spread to the blood. Infection of the blood causes illness, spread of the disease, and, ultimately, death. "This discovery is significant because it reveals a vital interaction between the malaria parasite and the person it infects. Before, we knew little about that interaction. The molecular details of our discovery will facilitate the design of new drugs and new vaccines," said Alexis Kaushansky, Ph.D., an Assistant Professor at the CIDR. The discovery was made through collaborative research among the laboratories of Stefan Kappe, Ph.D., Noah Sather, Ph.D., and Alexis Kaushansky, Ph.D. The combination of cross-disciplinary, collaborative research and technological approaches has allowed this type of discovery to be possible. As Louis H. Miller, M.D., Chief of the NIAID’s Malaria Cell Biology Section at the NIH, notes, "The findings on the liver receptor EphA2 for malaria parasite sporozoite invasion of liver cells is a critically important advance and might allow us to devise new strategies to block parasite infection." Dr. Miller was not involved in the reported research. The image shows the structure of the EphA2 protein.

Researchers from the Gladstone Institutes in San Francisco have shown, for the first time, that the unmutated BRCA1 (breast cancer 1) protein is required for normal learning and memory and is depleted by Alzheimer’s disease. BRCA1 is a key protein involved in DNA repair, and mutations that impair its function increase the risk for breast and ovarian cancer. The new study, published online today (November 30, 2015) in an open-access article in Nature Communications, demonstrates that Alzheimer’s disease is associated with a depletion of BRCA1 protein in neurons and that BRCA1 depletion can cause cognitive deficits. The article is titled ““DNA Repair Factor BRCA1 Depletion Occurs in Alzheimer Brains and Impairs Cognitive Function in Mice.” “BRCA1 has so far been studied primarily in dividing (multiplying) cells and in cancer, which is characterized by abnormal increases in cell numbers,” says first author Elsa Suberbielle, Ph.D., a research scientist at the Gladstone Institutes. “We were therefore surprised to find that it also plays important roles in neurons, which don’t divide, and in a neurodegenerative disorder [Alzheimer’s disease] that is characterized by a loss of these brain cells.” In dividing cells, BRCA1 helps repair a type of DNA damage known as double-strand breaks that can occur when cells are injured. In neurons, though, such breaks can occur even under normal circumstances in the absence of cell division, for example, after increased brain activity, as shown by the team of Gladstone scientists in an earlier study. The researchers speculated that, in brain cells, cycles of DNA damage and repair facilitate learning and memory, whereas an imbalance between damage and repair disrupts these functions. To test this idea, the scientists experimentally reduced BRCA1 levels in the neurons of mice.

A collaboration between researchers at the Babraham Institute and at the University of Manchester, both in the UK, has mapped the physical connections occurring in the genome to shed light on the parts of the genome involved in autoimmune diseases. Using a new technique, called Capture Hi-C, the team revealed novel insights into how changes in the genetic sequence can have a biological effect and increase the risk of disease. This new work was published online on November 30, 2015, in an open-access article in Nature Communications. The article is titled “Capture Hi-C Reveals Novel Candidate Genes and Complex Long-Range Interactions with Related Autoimmune Risk Loci.” The Human Genome Project provided much of the human DNA code and large population studies have since identified DNA sequence changes that are associated with a wide range of diseases, such as cancer, cardiovascular disease, and immune system disease. Because many of these changes fall outside the parts of the genome that contain protein-coding genes, understanding the biological relevance of the genetic change was akin to the party game ‘pin the tail on the donkey’ when it came to identifying the genes that these regions associated with. Understanding these associations represents the key to uncovering the causal genetic factors of disease. The new technique developed by researchers at the Babraham Institute identified a way to “freeze-frame” the genome and capture its three-dimensional conformation where the DNA folds to bring seemingly distant regions into close contact. This “snapshot” pinpoints where non-coding regulatory regions contact the genes that they control, often over large genomic distances.

Do you often take chances and yet still land on your feet? Then you probably have a well-developed brain. This surprising conclusion made as part of a project studying the brains of young male high and low risk-takers. The tests were carried out at the University of Turku in Finland under the direction of SINTEF (http://www.sintef.no/en/), using both the functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) techniques to measure activation-related and structural correlates of risky behavior, respectively. The aim of the project was to investigate the decision-making processes within the brains of 34 young men aged 18 or 19. Based on psychological tests, they were divided into two groups of low and high risk-takers, respectively. "We expected to find that young men who spend time considering what they are going to do in a given risk situation would have more highly developed neural networks in their brains than those who make quick decisions and take chances," says SINTEF researcher and behavioral analyst Dagfinn Moe, Ph.D. "This has been well documented in a series of studies, but our project revealed the complete opposite," he says. The surprising results have now been published in two articles, both published in the open-access journal PLOS ONE. One article is titled “Risk-Taking Behavior in a Computerized Driving Task: Brain Activation Correlates of Decision-Making, Outcome, and Peer Influence in Male Adolescents,” and was published online on June 8, 2015. The other article is titled “Brain Structural Correlates of Risk-Taking Behavior and Effects of Peer Influence in Adolescents,” and was published online on November 12, 2014.

Birds and humans look different, sound different, and evolved completely different organs for voice production. But now, new research published online on November 27, 2015 in an open-access article in Nature Communications reveals that humans and birds use the exact same physical mechanism to make their vocal cords move and thus produce sound. The article is titled “Universal Mechanisms of Sound Production and Control in Birds and Mammals.” "Science has known for over 60 years that this mechanism - called the myoelastic-aerodynamic theory, or in short the MEAD mechanism- drives speech and singing in humans. We have now shown that birds use the exact same mechanism to make vocalizations. MEAD might even turn out to be a widespread mechanism in all land-dwelling vertebrates", says lead author of the paper, Associate Professor Coen Elemans, Ph.D., Department of Biology, University of Southern Denmark. Co-authors of the new paper are from Emory University in the United States, Max Planck Institute for Ornithology in Germany, Palacky University in the Czech Republic, and additional collaborating institutions. Over the last year Dr. Elemans and his colleagues studied six different species of bird from five avian groups. The smallest species, the zebra finch, weighs just 15 grams, and the largest one, the ostrich, weighs in at 200 kilograms. All the studied birds were revealed to use the MEAD mechanism, just as humans do. In the human voice box (larynx), air from the lungs is pushed past the vocal cords, which then start moving back and forth sideways like a flag fluttering in the wind. With each oscillation, the larynx closes and opens, making the airflow stop and start, which creates sound pulses.

Fresh analysis of a 90-million-year-old reptile fossil is helping scientists solve an evolutionary puzzle - how snakes lost their limbs. The skull is giving researchers vital clues about how snakes evolved. Comparisons between CT scans of the fossil and modern reptiles indicate that snakes lost their legs when their ancestors evolved to live and hunt in burrows, which many snakes still do today. The findings show snakes did not lose their limbs in order to live in the sea, as was previously suggested. Scientists used CT scans to examine the bony inner ear of Dinilysia patagonica, a 2-meter-long reptile closely linked to modern snakes. These bony canals and cavities, like those in the ears of modern burrowing snakes, controlled the ancient reptile’s hearing and balance. The scientists constructed 3D virtual models to compare the inner ears of the fossils with those of modern lizards and snakes. Researchers found a distinctive structure within the inner ear of animals that actively burrow, which may help them detect prey and predators. This shape is not present in modern snakes that live in water or above ground. The new findings help scientists fill gaps in the story of snake evolution, and confirm Dinilysia patagonica as the largest burrowing snake ever known. The findings also offer clues about a hypothetical ancestral species from which all modern snakes descended, which was likely a burrower. The study, published recently in Science Advances, was supported by the Royal Society. Dr. Hongyu Yi, of the University of Edinburgh's School of GeoSciences, who led the research, said: "How snakes lost their legs has long been a mystery to scientists, but it seems that this happened when their ancestors became adept at burrowing.

A team of researchers led by scientists at Australia’s University of New South Wales (UNSW) has discovered how connections between brain cells are destroyed in the early stages of Alzheimer's disease - work that opens up a new avenue for research on possible treatments for the degenerative brain condition. "One of the first signs of Alzheimer's disease is the loss of synapses - the structures that connect neurons in the brain," says study leader, Dr. Vladimir Sytnyk, of the UNSW School of Biotechnology and Biomolecular Sciences. "Synapses are required for all brain functions, and particularly for learning and forming memories. In Alzheimer's disease, this loss of synapses occurs very early on, when people still only have mild cognitive impairment, and long before the nerve cells themselves die. "We have identified a new molecular mechanism which directly contributes to this synapse loss - a discovery we hope could eventually lead to earlier diagnosis of the disease and new treatments." The team studied a protein in the brain called neural cell adhesion molecule 2 (NCAM2) - one of a family of molecules that physically connects the membranes of synapses and help stabilise these long lasting synaptic contacts between neurons. The research was published online on November 27, 2015 in an open-access article Nature Communications. The article is titled “Aβ-Dependent Reduction of NCAM2-Mediated Synaptic Adhesion Contributes to Synapse Loss in Alzheimer’s Disease.” Using post-mortem brain tissue from people with and without the condition, they discovered that synaptic NCAM2 levels in the part of the brain known as the hippocampus were low in those with Alzheimer's disease.

Scientists extracted DNA from spider webs to identify the web's spider architect and the prey that crossed it, according to this proof-of-concept study published on November 25, 2015 in the open-access journal PLOS ONE by Charles C. Y. Xu from the University of Notre Dame, and colleagues. The article is titled “Spider Web DNA: A New Spin on Noninvasive Genetics of Predator and Prey.” Noninvasive genetic sampling enables biomonitoring without the need to directly observe or disturb target organisms. The authors of this study used three black widow spiders fed house crickets to noninvasively extract, amplify, and sequence mitochondrial DNA from their spider web samples, which identified both the spider and its prey to the species level. The detectability of spider DNA did not differ between assays and spider and prey DNA remained detectable at least 88 days after living organisms were no longer present on the web. The authors suggest that these results may encourage further studies that could lead to practical applications in conservation research, pest management, biogeography studies, and biodiversity assessments. However, further testing of field-collected spider webs from more species and habitats is needed to evaluate the generality of these findings. Xu says: "Sticky spider webs are natural DNA samplers, trapping nearby insects and other things blowing in the wind. We see potential for broad environmental monitoring because spiders build webs in so many places." The image shows a Southern black widow spider (Latrodectus mactans) with its prey house cricket (Acheta domesticus) trapped in spider web. (Credit: Scott Camazine).

Using the ground-breaking CRISPR/Cas9 gene editing technique, University of California scientists have created a strain of mosquitoes capable of rapidly introducing malaria-blocking genes into a mosquito population through its progeny, ultimately eliminating the insects' ability to transmit the disease to humans. This new model represents a notable advance in the effort to establish an anti-malarial mosquito population, which with further development could help eradicate a disease that sickens millions worldwide each year. To create this breed, researchers at the Irvine and San Diego campuses inserted a DNA element into the germ line of Anopheles stephensi mosquitoes that resulted in the genes preventing malaria transmission being passed on to an astonishing 99.5 percent of offspring. The transferred genes included dual anti-Plasmodium falciparum effector genes, a marker gene, and the autonomous gene-drive components. A. stephensi is a leading malaria vector in Asia. The study underlines the growing utility of the CRISPR method, a powerful gene editing tool that allows access to a cell's nucleus to snip DNA to either replace mutated genes or insert new ones. Results were published online on November 23, 2015 in PNAS. The article is titled “Highly Efficient Cas9-Mediated Gene Drive for Population Modification of the Malaria Vector Mosquito Anopheles stephensi.” "This opens up the real promise that this technique can be adapted for eliminating malaria," said Anthony James, Ph.D., Distinguished Professor of Molecular Biology & Biochemistry and Microbiology & Molecular Genetics at UC Irvine (UCI). For nearly 20 years, the James lab has focused on engineering anti-disease mosquitoes.

Swimming in a pool of syrup would be difficult for most people, but for bacteria like E. coli, it's easier than swimming in water. Scientists have known for decades that these cells move faster and farther in viscoelastic fluids, such as the saliva, mucus, and other bodily fluids they are likely to call home, but didn't understand why. Now, researchers from the University of Pennsylvania (Penn) School of Engineering and Applied Science and the Penn School of Arts & Sciences have come together to find an answer. Their findings could inform disease models and treatments, or even help design microscopic swimming robots. The study was led by Paulo Arratia, Ph.D., an Associate Professor in the Department of Mechanical Engineering and Applied Mechanics at Penn Engineering, and lab member Alison Patteson, a graduate student. Postdoctoral researcher Arvind Gopinath, Ph.D., a member of the Arratia lab, and Mark Goulian, Ph.D., the Edmund J. and Louise W. Kahn Endowed Term Professor of Biology in Penn Arts & Sciences, contributed to the study, which was published online on October 28, 2015 in an open-access article in Scientific Reports. The article is titled “Running and Tumbling with E. coli in Polymeric Solutions.” Experiments in the 1970s showed that, when in water, E. coli demonstrated what is known as "run and tumble" swimming. A bacterium would swim in a straight line, then tumble, or change direction in a random way. This is a good strategy for finding food, but it was unclear how that strategy would change in the more gelatinous fluids that E. coli tend to live in. "What's different now is that we can characterize the material properties of these fluids more precisely," Patteson said, "so we can connect changes in those properties to changes in the swimming behavior of the cells in a very systematic way.